The protective effect of coffee to the liver is explained by DNA methylation

Scientists from Europe on a sample of almost 16 thousand people
found a link between drinking coffee and tea and the change of DNA methylation. One
of the found sites was associated with a lower risk of developing obesity
liver. A study pre – published in the form of a Preprint on BioRxiv.

Statistical studies often linked the consumption of coffee
a certain benefit to health, for example, a lower risk of developing cognitive
disorders, diabetes or cardiovascular diseases. A few years ago
scientists on a sample of 400 thousand people also showed that two cups of coffee a day
(usually this corresponds to approximately 200 mg of caffeine) twice reduce the risk of
cirrhosis of the liver and death.

However, as from a biochemical point of view
coffee can mediate all of these effects is unclear. It was assumed, for example, that caffeine can affect cells
the heart muscle via protein p27
in the mitochondria, and the combination of the two components of coffee caffeine
and eicosanol-5-hydroxytryptamine, prevents protein aggregation in the neurons
and, thus, may delay the development of Parkinson’s disease.

Epidemiologists under the leadership of Mozena
Gambari (Mohsen Ghanbari)
from Erasmus University in Rotterdam (the Netherlands) held
a meta-analysis on a sample of 15789 participants between consumption of coffee and tea status
methylation of certain regions of their DNA. It turned out that the change
methylation of CpG islets
can affect gene expression and thereby mediate, for example, changes
lipid metabolism in the liver.

For the study, researchers participating in the consortium Cohort
for Heart and Aging Research in Genomic Epidemiology (CHARGE), combined
several existing European cohort studies and distributed them to participants
on two samples. The first came 9612 Europeans, and secondly (replicative)
included 6177 people of European and African descent. For all
participants were available data about food habits, including consumption of
caffeinated beverages, and blood samples.

In DNA from blood of study participants determined the methylation status of the
DNA regions enriched in pairs of nucleotides СpG. In such pairs cytosine (C) to
response to environmental conditions can metiliruetsa that is often associated with
change the expression of nearby genes. This mechanism is called epigenetic regulation.

Then the scientists analyzed the associations between the status
methylation of the known CpG sites
consumption of coffee and tea. For both groups it was discovered 11 of the coffee-dependent
plots, and two tea-dependent. Nine of the 11 coffee CpG sites were related to genes AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH. These genes, in turn,
associated with the pathways of metabolism of xenobiotics, biosynthesis of serine and
inflammatory response.

In addition, search in the database of the associations of methylation with expression
gene has forced researchers to pay attention to the plot cg14476101,
which was associated with changes in the gene expression of PHGDH, encoding the enzyme
phosphoglyceraldehyde. Previously it was shown that the change in methylation
this area is associated with lower risk of fatty liver.

To test the contribution of expression of PHGDH in liver function, the researchers
conducted an experiment on hepatic cell lines and selected two with the
highest and lowest gene expression level. It turned out that the expression of PHGDH in norm is positively correlated
with the expression of genes of lipid metabolism and its artificial shutdown reduces
also the expression of the latter.

The results of the experiment the researchers suggested that the consumption of
coffee may be associated with a reduced risk of liver disease, such as obesity
and cirrhosis, methylation plot cg14476101 and
mediated increase in the expression of PHGDH,
that improves lipid metabolism. However, authentic
causal relationship the authors could not be established.

That epigenetic changes can be caused by
diet, stress and even be transmitted to offspring, scientists know for a long time, but
most of these researches were conducted on model animals. Read more about
this can be found in our article “Genocide in the genome”.

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